Development and characterization of amphotericin B nanoemulsion-loaded mucoadhesive gel for treatment of vulvovaginal candidiasis

Despite being recognized as the “gold standard” for treating azole-resistant vulvovaginal candidiasis, amphotericin B (AmB), an amphoteric molecule, has not been widely used due to serious issues with solubility and permeability. In light of the aforementioned, the objective of the present study was to increase AmB’s therapeutic efficacy by formulating it into an o/w nanoemulsion (AmB-NE) system. Furthermore, to facilitate AmB-NE’s retention within the vaginal cavity, it was loaded into a mixture of Carbopol® 974P and Aloe vera-based gel (CA gel). Briefly, in the present study, a kinetically stable batch of formulated AmB-NE having a globule size of 76.52 ± 3.11 nm, PDI of 0.342 ± 0.032, and zeta potential of -22.32 ± 0.88 mV was incorporated into the CA gel base. This AmB-NE loaded gel (AmB-NE gel) exhibited a non-Fickian/anomalous diffusion from the hydrophilic matrix. The texture analysis of AmB-NE gel revealed that the prepared gel was a non-drip, soft, easy to spread, and sufficiently cohesive gel that could reside in the vaginal cavity, which was confirmed by our ex-vivo retention test, which revealed that AmB-NE loaded gel could stay in the vaginal cavity for approximately 11 h. Ex-vivo skin permeation studies revealed that AmB-NE is 4.26 times more permeable than AmB-coarse gel, implying that AmB-NE facilitates AmB entry into the vaginal epithelial layers. Furthermore, in-vivo vaginal lavage studies revealed that AmB-NE gel permeated 7.03-fold more than AmB-coarse gel. Prepared AmB-NE gel was stable in refrigerated condition and showed no histopathological toxicity. Thus, the present study suggests that AmB-NE gel could eliminate the existing problem of AmB and that it could serve as an alternative option to treat vulvovaginal candidiasis.

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Materials

Amphotericin B was obtained as a gift from Bharat Serum and Vaccines Ltd., Thane, India; Capmul MCM (glyceryl mono-dicaprylate) was supplied by Abitech Corporation through Indchem International, Mumbai, India; Cremophore RH 40 (PEG 35 castor oil ) was obtained from BASF India Ltd., Mumbai, India; and Transcutol HP (Highly purified diethylene glycol monoethyl ether) was obtained from Gattefosse, Lyon, France. The gelling agent, Carbopol 974P, was a kind gift from Noveon, Inc. Cleveland, OH, USA. Aloe vera gel was purchased from D. Jain’s Eco-friendly Industries, India. All other reagents used were of analytical grade.

Screening of oils

The solubility of AmB’s in various oils was evaluated by dissolving an extra amount of the drug in 5 mL of oils alone or in combination (Peceol, Capmul MCM, Capmul PG8, oleic acid, Labrafac, castor oil, isopropyl myristate (IPM), Peceol + castor oil, Peceol + Capmul MCM, Capmul MCM + castor oil) in stopper vials of 30 mL and mixed by a vortex mixer. The mixtures in the vials were allowed to reach equilibrium at 25 ± 1.0 °C for 48 h in an isothermal shaker [Nirmal International, India]. After equilibration, the samples were withdrawn and centrifuged for 15 min at 3000 rpm. The supernatant was filtered using a 0.45 μ membrane filter, and the concentrations of the AmB in oils were determined by High-Performance Liquid Chromatography (HPLC) [Agilent 1200, USA

Mrunal U. Patil, Amarjitsing Rajput, Veena S. Belgamwar, Shailesh S. Chalikwar, Development and characterization of amphotericin B nanoemulsion-loaded mucoadhesive gel for treatment of vulvovaginal candidiasis, Heliyon, 2022, e11489, ISSN 2405-8440, https://doi.org/10.1016/j.heliyon.2022.e11489.